Vva

o-methyltransferase Ti ^T

3-Methoxynorepinephrine ho

Epinephrine

FIGURE 2-24 Metabolic pathways for biosynthesis of the catechol estrogens (top) and their structural similarity to the catecholamines (bottom).

carbon-carbon bond, the B ring is opened up so that only the A, C, and D rings are intact. As discussed in Chapter 9, there are several families of vitamin D steroids (i.e., vitamin D2/ vitamin D3, vitamin D4) that depend on the structure of the secosteroid side chain. When the side chain is identical to that of cholesterol, then it is the naturally occurring form and belongs to the vitamin D3 family.

Vitamin D3 can be obtained dietarily or produced photochemically by sunlight from a precursor, 7-dehydrocholesterol, present in the skin. As documented in Fig. 2-25, vitamin D3 is known to be metabolized into a family of daughter metabolites.

The hormonally active forms that produce the spectrum of biological responses attributable to vitamin D3 are 1,25-dihydroxyvitamin D3 [l,25(OH)2D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3]. The principal form of vitamin D3 present in blood is 25-hydroxyvitamin D3 [25(OH)D3]. The enzymes in the liver that convert vitamin D3 into 25(OH)D3 are localized in both the mitochondria and the endoplasmic reticulum, while the enzymes in the kidney that catalyze the conversion of 25(OH)D3 into l,25(OH)2D3 or 24,25(OH)2D3 are located in the mitochondria of the proximal kidney tubule. All three enzymes contain cytochrome P450-type mixed-function oxidases. The other metabolites shown in Figure 2-25 are believed to be catabolites of the hormonally active forms.

G. Biosynthesis of Bile Acids

The conversion of cholesterol into bile acids takes place largely in the liver. In most mammals cholic acid (47) and chenodeoxycholic acid (48) (see Figure 2-11) are the principal products. Before excretion into the bile, the carbon-24 carboxyl of both steroids is conju

Haclone-Dj -24-COOH-D3 -tetranor-Dj -tetranor-23-COOH-D, -lactone-D3

(Catcitroic acid)

FIGURE 2-25 Metabolic pathway for the metabolism of vitamin D3 (cholecalciferol) into its daughter metabolites. The secosteroids presented in boldface are the physiologically relevant vitamin D compounds, while the other structures are believed to be catabolites of vitamin D3 (see Chapter 9).

Haclone-Dj -24-COOH-D3 -tetranor-Dj -tetranor-23-COOH-D, -lactone-D3

(Catcitroic acid)

FIGURE 2-25 Metabolic pathway for the metabolism of vitamin D3 (cholecalciferol) into its daughter metabolites. The secosteroids presented in boldface are the physiologically relevant vitamin D compounds, while the other structures are believed to be catabolites of vitamin D3 (see Chapter 9).

gated with the amino group of the amino acids taurine or glycine.

A key step in the production of the bile acids is the cleavage of the hydrocarbon side chain between carbon-24 and carbon-25. This does not occur by the lyase-type reactions associated with cholesterol side chain cleavage or production of androst-4-ene-3,17-dione (25). Instead, the removal of the three terminal carbon atoms is believed to proceed by a ^-oxidation mechanism similar to that occurring in fatty acid catabolism.

Additional key steps in the biosynthesis of bile acids involve (i) microsome-mediated hydroxylations at carbon-7 and carbon-12, (ii) epimerization of the 3/3-hydroxyl to a 3a-orientation (see Figure 2-11) and (iii) reduction of the A5-double bond so that the A: B ring junction is cis, as in 5/3-cholestane (22) (see Figure 2-5).

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Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

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